EMA Reviews Treatment Recommendations for Fabrazyme

LONDON, Oct. 22, 2010-The European Medicines Agency’s
Committee for Medicinal Products for Human Use (CHMP) has reviewed
its previous recommendations on the use of Fabrazyme (agalsidase
beta) during the ongoing supply shortage. This was triggered by an
increase in reported adverse events in patients treated with the
lower dose of Fabrazyme that has been introduced during the
shortage.

Fabrazyme is used to treat the rare, inherited enzyme-deficiency
disorder Fabry disease. Temporary treatment recommendations to
manage patients relying on this medicine have been in place since
the start of the supply shortage and have been regularly
updated.

The CHMP is now recommending that physicians switch back to
prescribing the full dose of Fabrazyme according to the authorised
product information, depending on the availability of enzyme
replacement therapy and the severity of the disease.

In making their recommendation, the Committee took the outcome
of a consensus group of experts in Fabry disease into account. The
group met twice in October 2010, and included physicians with
experience in Fabry disease and patient representatives working
together to prioritise patients with Fabry disease during the
ongoing supply shortage. The Committee also looked at spontaneous
reports of adverse events and data from the Fabry registry.

The CHMP noted that since the introduction of a lower dose of
Fabrazyme in June 2009, there has been a steady increase in the
number of reported adverse events, matching the increase in the
number of patients on the lower dose. At first, most of the events
were pain-related, soon followed by reports of events affecting the
heart, the central nervous system and the kidneys. This pattern
suggests a progression of Fabry disease. Recently, a decrease in
number of reported adverse events has been observed, which reflects
the fact that more patients have either been switched to Replagal
or have started receiving a full dose of Fabrazyme again. Despite
this, the Committee observed that a subgroup of patients seems to
be doing well on the lower Fabrazyme dose.

The CHMP also noted that monitoring plasma or urine GL-3 levels
does not appear to add value to the clinical management of the
patients while on a lower dose.

The updated CHMP temporary treatment recommendations for
Fabrazyme are as follows:

• Patients who require enzyme replacement therapy for Fabry
disease should be prescribed the authorised dose of either
Fabrazyme (1.0 mg/kg once every two weeks) or Replagal (0.2 mg/kg
once every two weeks).
•
• Low doses of Fabrazyme should be limited to those patients
who are stable and prefer to remain on a low dose.
•
• Patients and prescribers are advised that a deterioration of
the condition has been observed in patients on the lower dose.
Pain, cardiac manifestations and deafness are the usual
manifestations of Fabry disease progression.
•
These recommendations do not change the currently approved product
information for Fabrazyme.

The supply shortage of Fabrazyme began in June 2009 and was
caused by a series of manufacturing problems at the production site
in Allston Landing, in the United States of America. Because the
current productivity at Allston Landing is still lower than
expected, supply of Fabrazyme will not return to normal before the
second half of 2011, according to Genzyme.

The CHMP remains concerned about the continued supply shortages
of Genzyme’s medicines and is closely monitoring the
implementation of their improvement measures to prevent similar
manufacturing and quality problems in the future.

The Agency will make further updates as appropriate.

Notes:

• The CHMP assessment report on the supply shortage of
Fabrazyme between June 2009 and September 2010 will be published on
the European Medicines Agency’s website shortly.
•
• The treatment recommendations of the consensus group of the
experts in Fabry disease are in line with the currently authorised
product information of Fabrazyme, and will be published in a
peer-reviewed scientific journal
•
• The previous treatment recommendations of the CHMP for
Fabrazyme were made on 6 July 2010, following continued supply
shortage.
•
• Initially, the supply shortage for Fabrazyme was caused by
the shutting down of Genzyme’s production site in Allston
Landing, in the United States of America, for the sanitisation of
the bioreactors due to a viral contamination.